Stress Testing and Cardiac Magnetic Resonance

The purpose of this study is to better define the role of a comprehensive stress MRI (which includes myocardial perfusion imaging, optimized coronary imaging, and myocardial scar imaging) in medical practice and in patient health management. Information gathered from the healthy volunteers that participate in this study will be compared to information from the coronary artery disease patients in this study in order to help further our understanding.

Coronary artery disease is a major cause of morbidity and mortality in the United States. Currently, the presence of physiologically significant coronary disease is most commonly diagnosed using non-invasive imaging tests such as a nuclear stress test or an echo stress test. Unfortunately, nuclear stress tests require the use of ionizing radiation and have a limited spatial resolution. On the other hand, echo stress tests are dependent of adequate imaging windows. Adenosine stress testing combined with cardiac magnetic resonance (CMR) is a rapidly evolving technique for diagnosing significant coronary disease. It does not use ionizing radiation and has excellent image quality. In a recent meta-analysis of 14 studies with a total of 1,183 patients, the sensitivity and specificity of stress CMR for detecting significant coronary disease was 91% and 81%. Additionally, 2 studies have shown that patients with a normal stress CMR study have a <1% risk of having a cardiovascular event during the ensuing year. Another important advantage to stress CMR is the ability to fully quantify myocardial blood flow which may improve the diagnostic accuracy of stress CMR. In addition to perfusion imaging, CMR can directly visualize the coronary arteries, detect extremely small myocardial infarctions, and precisely measure the left ventricular function. Although adenosine stress CMR is a rapidly maturing test, several important challenges exist. First, many patients find it difficult to tolerate the common side effects of adenosine in the confined space of the MRI scanner. Secondly, many patients under the influence of adenosine and its side effects cannot adequately hold their breath during image acquisition making image interpretation more difficult and quantitative analysis very time consuming. Finally, because adenosine must be continuously infused during a contrast-enhanced stress CMR, 2 separate intravenous (I.V.) catheters are needed. Most of the undesirable effects of adenosine are mediated through the adenosine A(2B) and A(3) receptors; where as, its desired vasodilator effects are mediated through the A(2A) receptor. The FDA recently approved an adenosine A(2A) receptor specific stress testing agent called regadenoson which is administered as a 10 second bolus and has an improved side effect and safety profile when compared to adenosine. With its improved tolerability and ease of use, regadenoson is a more ideal stress testing agent to use with CMR. The purpose of this study is to determine whether a comprehensive regadenoson stress cardiac magnetic resonance study which includes myocardial perfusion imaging, optimized coronary imaging, and myocardial scar imaging provides incremental prognostic information over a clinical evaluation that includes nuclear stress testing.

Approximately 25 healthy volunteers will be recruited as controls. Scan will be done with regadenoson contrast.

Subjects in open label group will be given a single dose of regadenoson (0.4 mg, i.e. 5 ml i.v. bolus) as contrast.

Major adverse cardiovascular events, such as death, myocardial infarction, unstable angina, congestive heart failure, or cerebral vascular accident.

Inclusion Criteria: Suspected coronary artery disease Symptoms of possible coronary artery disease Exclusion Criteria: Acute ST-elevation myocardial infarction Second or third degree AV block Severe Renal Disease (Glomerular Filtration Rate (GFR) <30cc/min or hemodialysis) Contra-indications to MRI (i.e. Implantable Cardioverter Defibrillator (ICD), pacemaker, aneurysm clip, etc) Hemodynamic instability Inability to provide informed consent Severe claustrophobia Pregnancy Age <18 years

Hachamovitch R, Berman DS, Shaw LJ, Kiat H, Cohen I, Cabico JA, Friedman J, Diamond GA. Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction. Circulation. 1998 Feb 17;97(6):535-43. doi: 10.1161/01.cir.97.6.535. Erratum In: Circulation 1998 Jul 14;98(2):190.

McCrohon JA, Lyne JC, Rahman SL, Lorenz CH, Underwood SR, Pennell DJ. Adjunctive role of cardiovascular magnetic resonance in the assessment of patients with inferior attenuation on myocardial perfusion SPECT. J Cardiovasc Magn Reson. 2005;7(2):377-82. doi: 10.1081/jcmr-200053627.

Nandalur KR, Dwamena BA, Choudhri AF, Nandalur MR, Carlos RC. Diagnostic performance of stress cardiac magnetic resonance imaging in the detection of coronary artery disease: a meta-analysis. J Am Coll Cardiol. 2007 Oct 2;50(14):1343-53. doi: 10.1016/j.jacc.2007.06.030. Epub 2007 Sep 17.

Jahnke C, Nagel E, Gebker R, Kokocinski T, Kelle S, Manka R, Fleck E, Paetsch I. Prognostic value of cardiac magnetic resonance stress tests: adenosine stress perfusion and dobutamine stress wall motion imaging. Circulation. 2007 Apr 3;115(13):1769-76. doi: 10.1161/CIRCULATIONAHA.106.652016. Epub 2007 Mar 12.

Ingkanisorn WP, Kwong RY, Bohme NS, Geller NL, Rhoads KL, Dyke CK, Paterson DI, Syed MA, Aletras AH, Arai AE. Prognosis of negative adenosine stress magnetic resonance in patients presenting to an emergency department with chest pain. J Am Coll Cardiol. 2006 Apr 4;47(7):1427-32. doi: 10.1016/j.jacc.2005.11.059. Epub 2006 Mar 20.

Schwitter J, Wacker CM, van Rossum AC, Lombardi M, Al-Saadi N, Ahlstrom H, Dill T, Larsson HB, Flamm SD, Marquardt M, Johansson L. MR-IMPACT: comparison of perfusion-cardiac magnetic resonance with single-photon emission computed tomography for the detection of coronary artery disease in a multicentre, multivendor, randomized trial. Eur Heart J. 2008 Feb;29(4):480-9. doi: 10.1093/eurheartj/ehm617. Epub 2008 Jan 21.

Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS. Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation. 2003 Jun 17;107(23):2900-7. doi: 10.1161/01.CIR.0000072790.23090.41. Epub 2003 May 27.

Wang L, Jerosch-Herold M, Jacobs DR Jr, Shahar E, Detrano R, Folsom AR; MESA Study Investigators. Coronary artery calcification and myocardial perfusion in asymptomatic adults: the MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2006 Sep 5;48(5):1018-26. doi: 10.1016/j.jacc.2006.04.089. Epub 2006 Aug 17.

Patel AR, Epstein FH, Kramer CM. Evaluation of the microcirculation: advances in cardiac magnetic resonance perfusion imaging. J Nucl Cardiol. 2008 Sep-Oct;15(5):698-708. doi: 10.1016/j.nuclcard.2008.07.002. No abstract available.

Sakuma H, Ichikawa Y, Chino S, Hirano T, Makino K, Takeda K. Detection of coronary artery stenosis with whole-heart coronary magnetic resonance angiography. J Am Coll Cardiol. 2006 Nov 21;48(10):1946-50. doi: 10.1016/j.jacc.2006.07.055. Epub 2006 Oct 31.

Wagner A, Mahrholdt H, Holly TA, Elliott MD, Regenfus M, Parker M, Klocke FJ, Bonow RO, Kim RJ, Judd RM. Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study. Lancet. 2003 Feb 1;361(9355):374-9. doi: 10.1016/S0140-6736(03)12389-6.

Bellenger NG, Davies LC, Francis JM, Coats AJ, Pennell DJ. Reduction in sample size for studies of remodeling in heart failure by the use of cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2000;2(4):271-8. doi: 10.3109/10976640009148691.

Lieu HD, Shryock JC, von Mering GO, Gordi T, Blackburn B, Olmsted AW, Belardinelli L, Kerensky RA. Regadenoson, a selective A2A adenosine receptor agonist, causes dose-dependent increases in coronary blood flow velocity in humans. J Nucl Cardiol. 2007 Jul;14(4):514-20. doi: 10.1016/j.nuclcard.2007.02.016.

Ding S, Wolff SD, Epstein FH. Improved coverage in dynamic contrast-enhanced cardiac MRI using interleaved gradient-echo EPI. Magn Reson Med. 1998 Apr;39(4):514-9. doi: 10.1002/mrm.1910390403.

Christian TF, Rettmann DW, Aletras AH, Liao SL, Taylor JL, Balaban RS, Arai AE. Absolute myocardial perfusion in canines measured by using dual-bolus first-pass MR imaging. Radiology. 2004 Sep;232(3):677-84. doi: 10.1148/radiol.2323030573. Epub 2004 Jul 29.

Mor-Avi V, Akselrod S, David D, Keselbrener L, Bitton Y. Myocardial transit time of the echocardiographic contrast media. Ultrasound Med Biol. 1993;19(8):635-48. doi: 10.1016/0301-5629(93)90070-5.

Jerosch-Herold M, Wilke N, Stillman AE. Magnetic resonance quantification of the myocardial perfusion reserve with a Fermi function model for constrained deconvolution. Med Phys. 1998 Jan;25(1):73-84. doi: 10.1118/1.598163.

Spuentrup E, Katoh M, Buecker A, Manning WJ, Schaeffter T, Nguyen TH, Kuhl HP, Stuber M, Botnar RM, Gunther RW. Free-breathing 3D steady-state free precession coronary MR angiography with radial k-space sampling: comparison with cartesian k-space sampling and cartesian gradient-echo coronary MR angiography--pilot study. Radiology. 2004 May;231(2):581-6. doi: 10.1148/radiol.2312030451. Epub 2004 Mar 24.

Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med. 1979 Jun 14;300(24):1350-8. doi: 10.1056/NEJM197906143002402.

Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, Bundy J, Finn JP, Klocke FJ, Judd RM. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation. 1999 Nov 9;100(19):1992-2002. doi: 10.1161/01.cir.100.19.1992.

Bhave NM, Freed BH, Yodwut C, Kolanczyk D, Dill K, Lang RM, Mor-Avi V, Patel AR. Considerations when measuring myocardial perfusion reserve by cardiovascular magnetic resonance using regadenoson. J Cardiovasc Magn Reson. 2012 Dec 28;14(1):89. doi: 10.1186/1532-429X-14-89.